Cyanobacteria such as Synechococcus elongatus PCC 7942, Thermosynechococcus elongatus BP-1, and Synechocystis species strain PCC 6803 have an endogenous timing mechanism that can generate and maintain a 24 h (circadian) periodicity to global (whole genome) gene expression patterns. This rhythmicity extends to many other physiological functions, including chromosome compaction. These rhythmic patterns seem to reflect the periodicity of availability of the primary energy source for these photoautotrophic organisms, the Sun. Presumably, eons of environmentally derived rhythmicity--light/dark cycles--have simply been mechanistically incorporated into the regulatory networks of these cyanobacteria. Genetic and biochemical experimentation over the last 15 years has identified many key components of the primary timing mechanism that generates rhythmicity, the input pathways that synchronize endogenous rhythms to exogenous rhythms, and the output pathways that transduce temporal information from the timekeeper to the regulators of gene expression and function. Amazingly, the primary timing mechanism has evidently been extracted from S. elongatus PCC 7942 and can also keep time in vitro. Mixing the circadian clock proteins KaiA, KaiB, and KaiC from S. elongatus PCC 7942 in vitro and adding ATP results in a circadian rhythm in the KaiC protein phosphorylation state. Nonetheless, many questions still loom regarding how this circadian clock mechanism works, how it communicates with the environment and how it regulates temporal patterns of gene expression. Many details regarding structure and function of the individual clock-related proteins are provided here as a basis to discuss these questions. A strong, data-intensive foundation has been developed to support the working model for the cyanobacterial circadian regulatory system. The eventual addition to that model of the metabolic parameters participating in the command and control of this circadian global regulatory system will ultimately allow a fascinating look into whole-cell physiology and metabolism and the consequential organization of global gene expression patterns.
